1. Field of the Invention
The present invention generally relates to the control of a fluid flow over a surface, especially a sensing surface, within a flow cell of an analytical device and, more specifically, to the use of laminar flow cell techniques to position a fluid flow over desired surface areas within a flow cell.
2. Description of the Related Art
Flow cells are used extensively nowadays in a variety of analytical systems. Typically, the flow cell has an inlet opening, a flow channel and an outlet opening. A sample fluid to be investigated is introduced through the inlet opening, passes through the flow channel and leaves the flow cell through the outlet opening. In the flow channel, the sample fluid can be analyzed. The flow cell may have more than one inlet opening and optionally more than one outlet opening to permit desired manipulations of the flow pattern within the flow cell.
In one type of flow cell, the flow channel or channels contain a sensing surface, usually a substance layer to which a recognition element for an analyte in the sample is immobilized, typically a biochemical affinity partner to the analyte. When the analyte interacts with the recognition element, a physical or chemical change is produced on the sensing surface that can be detected by a detector, e.g. an optical, electrochemical or calorimetric detector. A flow channel may contain two or more sensing surfaces with different recognition elements.
The sensing surface or surfaces in the flow cell may be functionalized, or sensitized, in situ, i.e. within the flow cell. WO 90/05305 discloses a method for functionalizing a sensing surface having functional groups thereon by passing a reagent solution containing a bi- or polyfunctional ligand over the surface, the ligand having a function which immobilizes the ligand on the sensing surface and at least one more function which is exposed on the sensing surface for interaction with the analyte.
WO 99/36766 discloses methods and systems using hydrodynamic addressing techniques to allow immobilization of different ligands to discrete sensing areas within a single flow cell channel as well as to permit controlled sample delivery to such sensitized areas. In one embodiment, a so-called Y-cell having two inlet ports and one outlet port is used, wherein a laminar flow of a sample fluid (or sensitizing fluid in case of sensitization of the sensing surface) is provided adjacent to a laminar flow of a non-sensitizing fluid (e.g. a reference fluid) such that the fluids flow together over the sensing surface with an interface to each other. By adjustment of the relative flow rates of the two fluids the interface may be positioned laterally such that the sample fluid (or sensitizing fluid) contacts a desired discrete area of the sensing surface. In a variant, a so-called Ψ-cell having three inlet ports is used to sandwich the sample fluid (or sensitizing fluid) between two non-sensitizing fluid flows. A shortcoming of the methods and systems described in WO 99/36766 is, however, that selective contacting of a desired fluid with different areas of the sensing surface is only possible laterally, i.e. transversely to the flow path extension between the flow cell ends.
WO 97/01087 discloses a flow cell having an inlet opening for sample and an outlet opening. A further inlet opening for a reference fluid is provided which is positioned such that the reference fluid flows counter to the sample in the flow channel. In this way, the sample fluid may be kept away from the blocked volume occupied by the flowing reference fluid without the use of structural partitions in the flow channel. Typically, a detection layer containing sensitive recognition elements for an analyte extends the whole length of the flow cell channel, and the sample-free region of the flow channel can be used to generate a reference signal. However, the flow cell of WO 97/01087 has a fixed lengthwise extension of the sample region and the sample-free region, and requires that an outlet opening be located between the inlet openings for sample and reference fluid, respectively.
It would be desirable to be able to selectively and variably control the extension of a fluid flow in the longitudinal or normal direction of the flow cell. It would also be desirable to be able to use in this context a conventional type flow cell, such as the Y-cell or Ψ-cell mentioned above.
The present invention fulfills these needs and provides further related advantages.